Nuclear acting cellular proto-oncogenes have been studied in lung cancer lines and primary tumor specimens of all histologic types. These have led to the discovery of a series of DNA and RNA abnormalities showing that these play a key role in the pathogenesis of lung cancer. Recent work has led to the discovery of: new types of genetic changes including alterations in transcription and loss of attenuator function for myc family members; characterization of the protein products and biologic activity of the genes through transfection studies; and identification of the role of the c-jun gene in lung cancer. A considerable effort is going into the cloning and characterization of chromosomal deletion and translocation abnormalities in lung cancer cells using molecular genetic and cytogenetic techniques. There is a particular focus on the 3p deletion region, and the rb gene product which was found to be abnormal in the large majority of small cell lung cancers. A series of peptides produced by lung cancer cells including insulin-like and transferrin-like growth factors, opioid peptides, and their receptors, as well as GRP and other peptide hormone gene associated peptides have been identified as being autocrine growth factors involved in the pathogenesis of lung cancer. Genetic changes involved in the pathogenesis of human lung cancer including oncogene activation, chromosomal deletions, and autocrine growth factor production. To identify and characterize the genetic changes (somatic and constitutional) and mechanisms leading to the pathogenesis of lung cancer and to use this information to develop new methods to prevent, diagnose, and treat lung cancer.